Antibodies targeting M-CSF

Abstract

This disclosure generally relates to antibodies or antibody fragments which specifically bind to M-CSF. In particular antibodies and antibody fragments are disclosed which bind to M-CSF and which inhibit binding of M-CSF to the M-CSF receptor with an IC50 of 10 pM or less. The invention also relates to nucleic acids, vectors and host cells capable of expressing the antibodies or fragments thereof of the invention, pharmaceutical compositions comprising the antibodies or fragments thereof and uses of said antibodies or fragments thereof and compositions for treatment of specific diseases.

What is claimed is: 
     
       1. A method for inhibiting a bioactivity of M-CSF in a patient, said method comprising administering to the patient an antibody or antibody fragment which specifically binds to M-CSF, wherein said antibody or antibody fragment is able to inhibit the binding of M-CSF to the M-CSF receptor with an IC50 of 10 pM or less in a receptor binding inhibition assay comprising M-CSF at a final concentration of 12.5 pM,
 wherein the antibody or antibody fragment comprises: 
 (a) the HCDR1 region of SEQ ID NO:8, the HCDR2 region of SEQ ID NO:9, the HCDR3 region of SEQ ID NO:10, the LCDR1 region of SEQ ID NO:11, the LCDR2 region of SEQ ID NO:12 and the LCDR3 region of SEQ ID NO: 13, 
 (b) the HCDR1 region of SEQ ID NO:18, the HCDR2 region of SEQ ID NO:19, the HCDR3 region of SEQ ID NO:20, the LCDR1 region of SEQ ID NO:21, the LCDR2 region of SEQ ID NO:22 and the LCDR3 region of SEQ ID NO:23, or 
 (c) the HCDR1 region of SEQ ID NO:28, the HCDR2 region of SEQ ID NO:29, the HCDR3 region of SEQ ID NO:30, the LCDR1 region of SEQ ID NO:31, the LCDR2 region of SEQ ID NO:32 and the LCDR3 region of SEQ ID NO:33, and 
 wherein the bioactivity of M-CSF is M-CSF induced proliferation. 
 
     
     
       2. The method of  claim 1  wherein the antibody or antibody fragment comprises
 (a) the variable heavy region of SEQ ID NO:14 and the variable light region of SEQ ID NO:15, 
 (b) the variable heavy region of SEQ ID NO:24 and the variable light region of SEQ ID NO:25, or 
 (c) the variable heavy region of SEQ ID NO:34 and the variable light region of SEQ ID NO:35. 
 
     
     
       3. The method of  claim 1 , wherein the antibody or antibody fragment administered is of a lgG I subtype which has an effector function which is diminished compared to the wild type lgG I subtype. 
     
     
       4. The method of  claim 3 , wherein an aspartic acid residue at position 265 of said antibody (numbering according to the EU index) is exchanged for an alanine residue. 
     
     
       5. The method of  claim 1  wherein the antibody or antibody fragment administered is a monoclonal antibody or a polyclonal antibody. 
     
     
       6. The method of  claim 1  wherein the antibody or antibody fragment administered is a human, humanized or chimeric antibody. 
     
     
       7. The method of  claim 1  wherein the antibody or antibody fragment administered is cross-reactive to cynomolgus M-CSF, mouse M-CSF and/or rat M-CSF. 
     
     
       8. The method of  claim 1  wherein the patient is suffering from an inflammatory disorder. 
     
     
       9. The method of  claim 1  wherein the patient is suffering from an inflammatory disorder and administration of the antibody or antibody fragment alleviating inflammation in the patient. 
     
     
       10. The method of  claim 9  wherein the patient is suffering from rheumatoid arthritis.